Outline

Objective: Major oncologic pathways, such as the Wnt protein family and the Ras genes belong to oncogenes that play a significant role in tumour genesis pathways. In previous microarray analysis we showed a significant incidence of different gene expressions of Rab34 and WIF-1 in astrocytomas of WHO-grade III and IV. Both pathways maybe operative in early glioma tumour genesis. WIF-1 is a secreted antagonist of Wnt signalling and functions by direct binding to Wnt ligands in the extracellular space. Rab34 belongs to the group of Ras genes and is involved in various steps along the exocytic and endocytic pathways. Our current study analysed the incidence of WIF-1 and Rab34 expression in a larger number of tissue samples from astrocytomas of different WHO-grades.

Methods: To study possible differences in their expression we conducted semiquantitative two-step RT Real-Time PCR examinations on a total of 40 tissue samples of astrocytomas WHO-grade II to IV and first-time recurrent glioblastomas. Analysis was performed using the ABI™ Sequence Detection System ABI PRISMÂ® 7700 and Qiagen™ QuantiTectÂ® SYBRÂ® Green PCR Kits. According to the histological grading the arithmetic mean was calculated and compared.

Results: There is an immense uptake of WIF-1 in astrocytomas from grade II to grade III (+617%). Strong reduction of WIF-1 expression was present in glioblastoma when compared to astrocytomas grade III (-74%). Another down regulation of Wif-1-expression was seen in recurrent when compared to primary glioblastoma (-56%), their genetic expression was equivalent to astrocytomas grade II. Rab34 showed the highest expression in astrocytomas grade III and displayed an increase of 668% compared to the benign astrocytomas grade II. Moreover, Rab34-expression showed a doubled increase from primary to recurrent GBM (+101,97%).

Conclusions: Aberrant activation of the Wnt pathway indicates that loss of Wif-1 expression may be an early event in tumour genesis as demonstrated by other groups for higher tumour stages like urinary bladder or prostate cancer. Our results demonstrate continues down regulation of Wif-1 from grade III tumours over glioblastomas to their recurrences. Overexpressions of Rab GTPases are detected in various kinds of cancer. The increasing expression of Rab34 in all glioma grades supports the previously suggested role of tumour genesis for astrocytomas. The two factors Wif-1 and Rab34 might act in both the genesis and evolution of malignant gliomas.